The Pharmaceutical Research Of "Lizhiyan Dropping Pill"

Consisting of one medicinal herb,salvia plebeian,Salvia Plebeian Throat Dropping Pills has the function of clearing heat and removing toxicity,cooling the blood and dissipating blood stasis,and relieving cough and asthma.Clinically,it's mainly used for throat diseases,such as swollen sore throat,lung heat cough etc.The chemical compounds in salvia plebeian are primarily divided into diterpenes,triterpenes and flavonoid compounds.Researches show that the flavonoid compound in salvia plebeian is an effective constituent,which is anti-inflammatory,for the treatment of acute pharyngitis.Moreover,the salvia plebeian extractive that is extracted and purified with macroporous resin contains over 50%total flavonoid,conforming to the standard of five types of new drugs of traditional Chinese medicine.Total flavonoid ingredient is the main effective constituent of salvia plebeian for the treatment of throat diseases,but systematic and in-depth study on it is still unavailable currently,and nor is there a relevant national standard or industrial standard.At present,there is a big difference in the total flavonoid content of salvia plebeians of different origins,for the extract quality is influenced by various factors,like medicinal materials,manufacturing technique,quality analytical method etc.The constituent in salvia plebeian that has the highest content of flavonoid is Homoplantaginin,but currently,National Institute for Drug and Biological Product Control is unable to buy the reference substance of Homoplantaginin.Therefore,this paper provides a method to separate and purify Homoplantaginin of high purity,with the tested purity 98.5%.With the index of total flavonoid and Homoplantaginin,the paper studies the purification technology and testing method of salvia plebeian,and the HPLC fingerprint of salvia plebeian materials,salvia plebeian extract and Salvia Plebeian Throat Dropping Pills;with chemical and efficacy indexes,the paper probes into the anti-inflammatory efficacy of salvia plebeian and its effect in treating acute pharyngitis,offering theoretical and experimental basis that salvia plebeian total flavonoid can be used as the drug for chronic pharyngitis.According to fundamental researches,such as researches on the total flavonoid in salvia plebeian and its efficacy,pharmacokinetics,pharmacodynamics etc,salvia plebeian is extracted and separated and then is made into dropping pills,with modernized extraction and separation technology applied and advanced forming process and auxiliary material combined.The specific study includes the following aspects:1.Document research:guided by the theory of traditional Chinese medicine,the basis and significance of this paper are comprehensively expounded;meanwhile,the chemical constituents,pharmacological action and clinical application are concluded and summarized.2.Preliminary experiment:the pros and cons of water extraction and alcohol extraction of salvia plebeian were compared,with the transfer rate,purity and pharmacodynamics of total flavonoid and Homoplantaginin as the indexes.Results showed that the transfer rate and purity of total flavonoid of alcohol extraction was higher than that of water extraction.Moreover,when it came to the effect of the two intermediates obtained after the purification,the intermediate of alcohol extraction had a better anti-inflammatory effect on mice with ear swelling caused by dimethylbenzene and model rats with acute pharyngitis.Thus,the experiment finally determined alcohol extraction and macroporous resin purification as the extraction and purification method of salvia plebeian.3.Preparation technology research:with the assaying of total flavonoid and Homoplantaginin as the index,single factor experiment and orthogonal experiment were applied,and extraction and purification were optimized.The result was:a prescription of medicinal materials was weighed up and extracted with 60%alcohol,6 times of alcohol per time.It's decocted for 3 times,1 hour per time.The filtrate was merged after filtering or high-speed centrifugation,the ethanol was vacuum concentrated(60-70 ?)and recovered until 0.8 g/ml,1 g crude drugs for 1 ml of resin.After sample application,flush with double column volume of water,and then elute with 75%ethanol of 7 times column volume.Vacuum and concentrate the collected resin eluent to dense paste,after vacuum drying,the salvia plebeian intermediate was obtained after being grinded through 120 mesh sieves.With the qualified intermediate obtained in the extraction and purification of the crude drugs as the raw material,types and ratios of the auxiliary materials needed in the forming process of the preparation was optimized through single factor experiment and orthogonal experiment.And the final determined forming process was:the oil bath temperature was 90?,the drip tray temperature was 95 ? and the coolant temperature was 15-?;weigh up 3 intermediates successively:4 PEG4000 and 8 PEG6000.With dimethicone as the coolant,the drugs and matrixes were averagely intermingles in the water bath where the temperature was 85 ? and then put into the pill dropping machine to be made into dropping pills with the dropping speed adjusted.The dimethicone remained on the surface of the dropping pills was washed away with petroleum ether,and the sample was obtained by low temperature drying.4.Quality standard research:the quality standard research of salvia plebeian,the intermediate of salvia plebeian and Salvia Plebeian Throat Dropping Pills has been conducted,including water content test,total flavonoid content test,Homoplantaginin content test,thin-layer chromatography of fingerprint and the preparation,and regular project check,and finally the preparation standard(draft)was concluded.5.Primary pharmacokinetics research:the absorption condition of Homoplantaginin in SD rats was studied after intragastric administration.The result was:Homoplantaginin was rapidly absorbed in rats,and it reached the peak after about 30 min.A double peak phenomenon of Homoplantaginin occurred in the rats.